RGD侧链环肽 | 226559-04-2

• 物质功能分类: 生物化工 - 多肽
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: RGD侧链环肽
• 英文名称: c(-Arg(Pbf)-Gly-Asp(OtBu)-DPhe-Lys-)
• 英文别名: c[R(pbf)GD(tBu)fK]；cyclo(-Arg(Pbf)-Gly-Asp(OtBu)-D-Phe-Lys-)；Protected cyclic RGDfK(NH2)；tert-butyl 2-[(2S,5R,8S,11S)-8-(4-aminobutyl)-11-[3-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]propyl]-5-benzyl-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetate
• CAS: 226559-04-2
• 化学式: C₄₄H₆₅N₉O₁₀S
• 分子量: 912.12
• InChiKey: SPXAFBLEZPVDOP-SSNHPIBPSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  64
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  300
• 氢给体数：
  8
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  RGD侧链环肽 在 三异丙基硅烷 、 三乙胺 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 cyclo(Arg-Gly-Asp-D-Phe-Lys)-Biotin
  参考文献：
  名称：

  Chemical Functionalization of Bioceramics To Enhance Endothelial Cells Adhesion for Tissue Engineering

  摘要：

  To control the selective adhesion of human endothelial cells and human serum proteins to bioceramics of different compositions, a multifunctional ligand containing a cyclic arginine-glycine-aspartate (RGD) peptide, a tetraethylene glycol spacer, and a gallate moiety was designed, synthesized, and characterized. The binding of this ligand to alumina-based, hydroxyapatite-based, and calcium phosphate-based bioceramics was demonstrated. The conjugation of this ligand to the bioceramics induced a decrease in the nonselective and integrin-selective binding of human serum proteins, whereas the binding and adhesion of human endothelial cells was enhanced, dependent on the particular bioceramics.

  DOI：

  10.1021/jm301092r
• 作为产物：
  描述：

  H-Asp(OtBu)-D-Phe-Lys(Z)-Arg(Pbf)-Gly-OH 在 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 甲酸铵 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 12.0h， 生成 RGD侧链环肽
  参考文献：
  名称：

  Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells

  摘要：

  肿瘤细胞对凋亡的耐受性是对化疗产生抗药性的主要机制。事实证明，Smac/DIABLO 拟效物能有效克服因抗凋亡蛋白 XIAP、cIAP1 和 cIAP2 过度表达而导致的癌症细胞对凋亡的耐药性。在这项研究中，我们描述了一种能够选择性激活癌细胞凋亡的双靶向肽。该复合物由荧光周期性介孔有机硅纳米粒子组成，该粒子携带与 αvβ3 整合素配体结合的 Smac/DIABLO 短序列。与αvβ3阴性的Ht29细胞相比，双靶向肽@PMO在αvβ3阳性的HeLa细胞中显示出明显更高的毒性。@PMO 与奥沙利铂联用时，在一组 αvβ3 阳性癌细胞中显示出协同效应，而 XIAP 过表达或整合素 β3 沉默可克服其毒性。αvβ3阳性细胞对该分子的成功吸收，使@PMO有望重新使许多癌症类型的细胞对凋亡敏感。

  DOI：

  10.3389/fphar.2023.1237478

文献信息

• Purification-Free Method for Preparing Technetium-99m-Labeled Multivalent Probes for Enhanced in Vivo Imaging of Saturable Systems
  作者：Yuki Mizuno、Tomoya Uehara、Hirofumi Hanaoka、Yota Endo、Chun-Wei Jen、Yasushi Arano

  DOI：10.1021/acs.jmedchem.6b00024

  日期：2016.4.14

  yields. This complex exhibited higher integrin αvβ3 binding affinity than its unlabeled monovalent ligand, primarily due to its multivalency. This compound visualized a murine tumor without removing unlabeled ligands, while a 99mTc-labeled monovalent probe derived from a monovalent ligand could not. The metal coordination-mediated synthesis of radiolabeled multivalent probes thereby can be a useful

  金属放射性核素为分子成像提供靶标特异性的放射性标记探针，其放射化学产率足以无需纯化即可施用于受试者。但是，注射液中未标记的配体可以与放射性标记的探针竞争靶向分子，最终需要进行标记后的纯化。在这里，我们描述了一种“ 1至3”设计，以利用tech 99m（99m Tc）的固有配位特性来规避该问题。使具有异腈作为配位基团的一价RGD配体（CN-RGD）与[ 99m Tc（CO）3（OH 2）3 ] +反应以制备[ 99m Tc（CO）3（CN-RGD）3 ] +的放射化学产率超过95％。这种复杂的表现出整合素α更高v β 3比其未标记的配体的单价主要是由于其多价性结合亲和力。该化合物在不去除未标记配体的情况下观察到了鼠类肿瘤，而源自单价配体的99m Tc标记的单价探针则不能。因此，金属配位介导的放射性标记多价探针的合成可以成为制备现成的，标有99m Tc和其他感兴趣的金属放射性核素的靶标特异性探针的有用方法。
• TRAP, a Powerful and Versatile Framework for Gallium-68 Radiopharmaceuticals
  作者：Johannes Notni、Jakub Šimeček、Petr Hermann、Hans-Jürgen Wester

  DOI：10.1002/chem.201103503

  日期：2011.12.23

  A veritable gallium TRAP: Triazacyclononane‐phosphinic acid chelators (TRAP) form highly stable complexes with Ga3+ (see figure) extremely efficiently over a wide pH range. Homo‐ and heteromultimeric bioconjugates can be synthesized in a straightforward manner, all of which renders TRAP a chelator with ideal properties for 68Ga positron emission tomography (PET) imaging agent elaboration.

  真正的镓TRAP：三氮杂双环壬烷次膦酸螯合剂（TRAP）在很宽的pH范围内与Ga 3+形成高度稳定的络合物（见图）。可以通过简单的方式合成同聚和异聚生物共轭物，所有这些都使TRAP成为具有理想性质的螯合剂，可用于68 Ga正电子发射断层扫描（PET）成像剂的制备。
• Coordination-Mediated Synthesis of ⁶⁷Ga-Labeled Purification-Free Trivalent Probes for in Vivo Imaging of Saturable Systems
  作者：Holis A. Holik、Tomoya Uehara、Soki Nemoto、Takemi Rokugawa、Yuumi Tomizawa、Ayako Sakuma、Yuki Mizuno、Hiroyuki Suzuki、Yasushi Arano

  DOI：10.1021/acs.bioconjchem.8b00337

  日期：2018.9.19

  A large excess of unlabeled ligands over gallium-67 (67Ga) provides 67Ga-labeled probes with high radiochemical yields in a short reaction time. However, the unlabeled ligands hinder target accumulation of radiolabeled probes by competing for target molecules. To circumvent the problem, we investigated the way to prepare 67Ga-labeled multivalent probes from monovalent ligands. The reaction of a bi- or tridentate ligand with [67Ga]Ga-citrate resulted in 67Ga-labeled probes of insufficient stability. However, the reaction of [67Ga]Ga-citrate with a mixture of RGD-conjugated salicylaldehyde and triamine provided a 67Ga-labeled trivalent probe with stability sufficient for in vivo applications. Since the free Schiff base ligand decomposed rapidly upon injection, the 67Ga-labeled trivalent probe visualized the murine tumor without postlabeling purification, which was not achieved with a 67Ga-labeled trivalent probe from a trivalent ligand. These findings indicate the availability of Schiff base ligands to prepare 67Ga-labeled trivalent probes by a simple radiolabeling procedure.

  大量未标记的配体相对于镓-67 (67Ga) 的过量提供了在短时间内获得高放射化学产率的67Ga标记探针。然而，未标记的配体通过竞争靶分子而妨碍了放射性标记探针的靶向聚集。为了解决这个问题，我们研究了如何从单价配体制备67Ga标记的多价探针。双齿或三齿配体与[67Ga]Ga-柠檬酸的反应产生的67Ga标记探针稳定性不足。然而，[67Ga]Ga-柠檬酸与RGD结合的水杨醛和三胺混合物的反应则提供了一种具有足够稳定性用于体内应用的67Ga标记三价探针。由于游离的希夫碱配体在注射后迅速降解，因此67Ga标记的三价探针能够在没有后标记纯化的情况下可视化小鼠肿瘤，而这在由三价配体制备的67Ga标记三价探针中无法实现。这些发现表明希夫碱配体可通过简单的放射性标记程序制备67Ga标记的三价探针。
• Benzylprotected aromatic phosphonic acids for anchoring peptides on titanium
  作者：Jörg Auernheimer、Horst Kessler

  DOI：10.1016/j.bmcl.2005.10.018

  日期：2006.1

  improved and earlier osseous integration of implants in vivo. Titanium, an often used material in implant surgery, can be easily coated by peptides bearing phosphonic acid groups. We report here, the synthesis of benzyl protected phosphonic acids suitable for solid-phase peptide synthesis (SPPS), which can be easily deprotected with TFA.

  生物相容性涂层的开发是一个持续的问题。模仿成骨细胞对细胞外基质的生理粘附过程可改善成骨细胞在体外的细胞粘附，并导致体内植入物的骨整合得到改善和更早的骨整合。钛是植入手术中常用的材料，很容易被带有膦酸基团的肽包被。我们在这里报告，适合固相肽合成（SPPS）的苄基保护的膦酸的合成，可以很容易地用TFA脱保护。
• Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions
  作者：Daniel J. Welsh、David K. Smith

  DOI：10.1039/c1ob05241a

  日期：——

  This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC50 of 125 μM (375 μM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 μM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.

  本文比较了组织配体阵列以结合整合素的共价和非共价方法。在共价策略中，线性 RGD 肽与第一代和第二代树枝状配体共轭，并使用荧光偏振竞争分析法证明第一代化合物能最有效地结合整合素，EC50 为 125 μM（每个肽单位为 375 μM）。因此，即使浓度高达 1 mM，这种树枝状化合物也比不与整合素结合的单价配体有效得多。不过，第二代化合物的效果明显较差，这表明在这种情况下，多价配体存在一个最佳配体密度。在多价性的非共价方法中，同样的 RGD 肽被疏水的 C12 链功能化，从而产生了一种经证明能够自组装的脂肽。这种脂肽在浓度为 200 ¼M 时就能与整合素有效结合。因此，这些结果表明，在实现配体阵列的多价组织方面，共价（树枝状）和非共价（胶束自组装）方法的效率相当。